The photocatalytic disinfection capability of the natural semiconducting mineral sphalerite is studied here for the first time. Natural sphalerite can completely inactivate 1.5 × 10(7) cfu/mL E. coli K-12 within 6 h under visible light irradiation. The photocatalytic disinfection mechanism of natural sphalerite is investigated using multiple scavengers. The critical role that electrons play in bactericidal actions is experimentally demonstrated. The involvement of H(2)O(2) in photocatalytic disinfection is also confirmed using a partition system combined with different scavengers. Moreover, the photocatalytic destruction of bacterial cells is observed through transmission electron microscopic analysis. A catalase activity study reveals that antioxidative enzyme activity is high in the initial stage of photocatalytic disinfection but decreases with time due to damage to enzymatic functioning. Natural sphalerite is abundant and easy to obtain and possesses excellent visible-light photocatalytic activity. These superior properties make it a promising solar-driven photocatalyst for large-scale cost-effective wastewater treatment.